Transsynaptic degeneration in the superficial dorsal horn after sciatic nerve injury: effects of a chronic constriction injury, transection, and strychnine

Abstract

The lumbar and cervical spinal dorsal horns of adult rats with a chronic (8 days) constriction injury of the sciatic nerve on one side (and a sham operation on the other) were examined for signs of transsynaptic degeneration. The incidence of neurons with signs of degeneration (pyknosis and hyperchromatosis; 'dark neurons') was significantly increased in the lumbar dorsal horn on both sides. The ipsilateral lumbar increase was significantly greater than the contralateral increase. There was no increase in the incidence of dark neurons in the cervical dorsal horns of the same rats. The distribution of lumbar dark neurons was similar bilaterally. The majority of the dark neurons were found in the sciatic nerve's territory in laminae I-II. A second group of rats received the same surgery but in addition received a series of 7 daily subconvulsive doses of strychnine. Dark neurons were again found bilaterally (with ipsilateral predominance) in the sciatic nerve's territory in lumbar laminae I-II, but the incidence was significantly greater than that found in the group that did not receive strychnine. The same result was obtained in a third group of strychnine-treated rats when the sham operation was omitted. Thus the appearance of contralateral dark neurons is not dependent on unintentional nerve damage created by the sham procedure. An additional group of rats was sacrificed 8 days after receiving a unilateral sciatic nerve transection, a contralateral sham operation, and the 7 daily strychnine injections. There was no increase in the incidence of dark neurons in any of these rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of Central Glucocorticoid Receptors after Peripheral Nerve Injury Contributes to Neuropathic Pain Behaviors in Rats

“…Although the antiinflammatory effects of corticosteroids could be beneficial under such circumstances, our results indicate that an unexpected adverse effect of GR activation within the CNS could contribute to the neural mechanisms of neuropathic pain behaviors. Second, neuronal degeneration within the spinal cord dorsal horn occurs after peripheral nerve injury (Sugimoto et al, 1990;Mao et al, 1997;Moore et al, 2002), and recent studies have indicated detrimental effects of GR agonists on NMDA-induced neuronal degeneration (Abraham et al, 2000) and in neuronal apoptosis during autoimmune-related inflammation (Diem et al, 2003). Thus, actions of central GRs could potentially worsen neuronal degeneration induced by peripheral nerve injury.…”

Blocking Caspase Activity Prevents Transsynaptic Neuronal Apoptosis and the Loss of Inhibition in Lamina II of the Dorsal Horn after Peripheral Nerve Injury

“…Peripheral nerve injury produces apoptosis in the dorsal horn of the spinal cord (Sugimoto et al, 1990;Azkue et al, 1998;Whiteside and Munglani, 2001;Moore et al, 2002). In the superficial dorsal horn (laminas I-III), interneurons containing the transmitters GABA and glycine produce presynaptic and postsynaptic inhibition (Malcangio and Bowery, 1996).…”

Loss of Neurons from Laminas I-III of the Spinal Dorsal Horn Is Not Required for Development of Tactile Allodynia in the Spared Nerve Injury Model of Neuropathic Pain

“…Evidence for this hypothesis includes the following observations: (1) loss of GABAergic or glycinergic inhibition within the dorsal horn leads to allodynia (Yaksh, 1989) and a lowered threshold for withdrawal reflexes (Sivilotti and Woolf, 1994); (2) there is a reduction in the level of GABA (Castro-Lopes et al, 1993;Ibuki et al, 1997;Eaton et al, 1998) and its synthesizing enzyme glutamate decarboxylase (Moore et al, 2002) in the ipsilateral dorsal horn after nerve injury; (3) "dark neurons" (Sugimoto et al, 1990) and apoptotic cells labeled with the terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) method (Kawamura et al, 1997;Azkue et al, 1998;Whiteside and Munglani, 2001;Moore et al, 2002;de Novellis et al, 2004) have been detected in the dorsal horn after various types of nerve injury; (4) a substantial reduction of primary afferent-evoked IPSCs in lamina II neurons has been reported in neuropathic models (but not after sciatic nerve transection) and was thought to result from a presynaptic mechanism involving reduction of GABA release (Moore et al, 2002). Although most studies of apoptosis in the dorsal horn after nerve injury have not identified the cell types involved, Moore et al (2002) reported that in the spared nerve injury (SNI) model (Decosterd and Woolf, 2000), ϳ10% of TUNEL-positive cells were neuronal.…”